Associations between pharmacy choice and influenza vaccination: Mail order vs community pharmacy users

BACKGROUND: Despite the effectiveness of vaccines, US adult vaccination rates remain low. This is especially true for the influenza vaccine, which is recommended annually and widely available. The accessibility of community pharmacies as convenient places to receive influenza vaccines has been shown to increase uptake. However, use of mail order pharmacies may reduce in-person pharmacist encounters and reduce the likelihood that users receive annual influenza vaccines. OBJECTIVE: To determine the association between the type of pharmacy a patient uses and their likelihood of receiving an influenza vaccine. METHODS: This cross-sectional cohort study used the 2018 Medical Expenditure Panel Survey to observe noninstitutionalized US adult pharmacy users. Pharmacy type was dichotomized into community use only vs any mail order pharmacy use. Multivariable weighted logistic regression was used to identify associations between the type of pharmacy used and influenza vaccination, adjusting for sociodemographic, health status, and health care access and utilization confounders. All analyses were stratified by age (< 65 and ≥ 65 years). RESULTS: The aged younger than 65 years and aged 65 years and older samples had 8,074 and 4,037 respondents who represented 95,930,349 and 40,163,276 weighted observations, respectively. Compared with community pharmacy users, mail order users were more likely to be aged 65 and older, be White, have high income, and have a usual source of care (P < 0.0001). Adjusted odds ratios (AORs) for influenza vaccination were significantly lower among community pharmacy users than mail order users among individuals aged younger than 65 years (AOR=0.71; 95% CI = 0.580.87) but was not significant among those aged 65 years and older (AOR = 0.87; 95% CI = 0.69-1.09). CONCLUSIONS: Community pharmacy users aged younger than 65 years are less likely to receive the influenza vaccine than their mail order pharmacy user counterparts. These counterintuitive results could be caused by residual confounding due to differences in factors that influence pharmacy use type and vaccination likelihood. Further exploration is needed to account for differences between these populations that independently drive vaccination choice.


Plain language summary
Many people in the United States do not get flu shots. Community pharmacies giving vaccines make it easier to get a flu shot. Using a mail order pharmacy could decrease the chance that people get their flu shots. However, community pharmacy users are actually less likely than mail order users to get flu shots. People who use community pharmacies are prime targets for flu shot-related public health intervention.
Before the COVID-19 pandemic, an estimated 90,000 US residents died of vaccine-preventable illnesses including influenza and pneumococcal disease every year. 1 Not only can vaccines decrease illness-related morbidity and mortality, they are one of the most cost-effective measures against infectious diseases, preventing more than 8,000 deaths, 109,000 hospitalizations, 3 million medical visits, and 7 million illnesses in the 2017-2018 flu season alone. [2][3][4][5] Yet, during the 2018-2019 flu season, less than half of United States adults (45.3%) received an influenza vaccination. 6 Low rates of adult vaccination uptake result in avoidable economic losses to individuals and society in the billions annually. 7 Many who desire to receive their vaccine encounter barriers including lack of provider access and knowledge about the vaccine, high cost, and lack of job flexibility and time off to seek health care. 3 Fortunately, a major avenue that has increased vaccine access for many patients, particularly influenza vaccination, is allowing the community pharmacy to serve as an immunization access point. 8,9 With all 50 states now allowing pharmacists to administer vaccinations, adult influenza vaccination rates have slowly followed an upward trajectory, with the community pharmacy becoming the second most used site for influenza vaccination among adults. 3,6,8,9 More than 90% of Americans live within 5 miles of a community pharmacy. 10 Not only are community pharmacies numerous, they offer extended hours, often provide more cost-effective vaccination services and greater convenience than traditional outpatient and doctor office visits, provide access to one of the most trusted health care professionals, and are able to reach underserved communities. 4,10,11 Patients that use community pharmacies, on average, visit their community pharmacist 1.5-2 times as often as their physician or other qualifying health practitioners. 12,13 In fact, each year that a person is exposed to pharmacybased immunization services increases their odds of receiving influenza vaccinations and visiting a community pharmacy to do so, with an additional 6.2 million additional influenza vaccinations being attributed to pharmacy-based immunizations annually. 14, 15 Most recently, 187.4 million COVID-19 vaccine doses were administered and reported among 21 community pharmacy partners collaborating with the US federal government to provide vaccinations nationwide as of December 2021, demonstrating the crucial role of community pharmacies to population health and immunization efforts. 16 Nevertheless, the steady rise in use of mail order pharmacies-those that usually communicate with the patient remotely and mail prescriptions directly to them-could reduce the exposure of patients to community pharmacies as a source for vaccinations. Between 1996 and 2018, the prevalence of mail order pharmacy use increased from 6.9% to 10.3%, with the average annual mail order prescriptions per patient increasing from 10.7 to 20.5. 17 Furthermore, with the additional spike in use of remote medical services, such as telehealth medicine because of COVID-19, use of mail order pharmacies is becoming increasingly popular. 18 Mail order pharmacies are not a new phenomenon. In fact, mail order pharmacy use has been associated with positive patient health outcomes, improved medication adherence, and decreased patient out-of-pocket pharmacy-related costs. [19][20][21][22] However, as mail order pharmacies increase in popularity and employers and insurance plans incentivize the use of these pharmacies into their benefits plans, a new trend in immunization rates could emerge. 17,23 It is possible that decreased in-person interactions with pharmacists owing to increased mail order pharmacy use could reduce the opportunity and ability for individuals to receive their annual influenza vaccine. Alternatively, the higher use of mail order pharmacies may not influence a person's likelihood of receiving their vaccination.
Previous studies characterized mail order pharmacy users and separately observed predictors of vaccination likelihood in select subpopulations; however, none have studied the potential influence of pharmacy use type on influenza vaccination or how additional patient factors can impact their correlative relationship using a nationally representative adult sample. 17,[24][25][26][27][28] As such, the objective of this study was to examine the association between pharmacy use type and the likelihood of influenza vaccination in US adults. odds ratios (AORs) for influenza vaccination were significantly lower among community pharmacy users than mail order users among individuals aged younger than 65 years (AOR = 0.71; 95% CI = 0.58-0.87) but was not significant among those aged 65 years and older (AOR = 0.87; 95% CI = 0.69-1.09).
CONCLUSIONS: Community pharmacy users aged younger than 65 years are less likely to receive the influenza vaccine than their mail order pharmacy user counterparts. These counterintuitive results could be caused by residual confounding due to differences in factors that influence pharmacy use type and vaccination likelihood. Further exploration is needed to account for differences between these populations that independently drive vaccination choice. vaccine in the past 12 months." Participants who responded affirmatively are considered to have received the vaccine; all other responses were considered to not have received the vaccine.
The key exposure of interest in this study is the type of pharmacy that is used by participants in the sample (variable name: PHARTPn). This information was retrieved in the data using one of 5 defined "pharmacy type" variables that identify the types of pharmacy providers from which the participant's prescribed medicines were received. This is a self-reported variable and participants respond based on whether they have used any of these types of pharmacies within the interview panel period. The possible types of pharmacies include the following: (1) "mail order," (2) "another store," (3) "HMO/clinic/hospital," (4) "drug store," and (5) "online." Consistent with previous literature, mail order and online designations were considered mail order, drug stores and other stores were considered community, and those who solely used HMO/clinical/hospital were not included; the community pharmacy cohort was defined as having no exposure to mail order pharmacy, and the mail order pharmacy cohort was defined as having any exposure to mail order pharmacy. 24,25 Additional measures captured in the study included sociodemographic, health-related, health services utilization, and health status variables. Sociodemographic variables included age, sex, family income (as a percentage of federal poverty level), region, race and ethnicity, and education. Health-related variables included a diagnosis of cancer, diabetes, asthma, and/or heart disease and patient perception of their health. Health services access and utilization variables included insurance type, annual paid leave, and travel time to their usual care provider. Weighted estimates for all variables were used for analyses.

ANALYTICAL PLAN
This cross-sectional cohort study used descriptive statistics to observe the distribution of the data across the 2 cohorts. Weighted logistic regression was used to observe the unadjusted association between the pharmacy choice and vaccination status, whereas multivariable weighted logistic regression identified associations between the type of pharmacy used and influenza vaccination status, adjusting for known confounders including sociodemographic, health status, and health services access and utilization factors. Finally, the sample was stratified by age into patients aged younger than 65 years (< 65) and those aged 65 years and older (≥ 65) owing to differences in access to health care, health insurance availability, and susceptibility to vaccine-seeking behaviors. 31-34 Respondents with missing data in the exposure, outcome, or covariate variables were not

DATA SOURCE
The latest available data from the Medical Expenditure Panel Survey (MEPS), a nationally representative survey of noninstitutionalized US citizens, from 2018 was used for this study. The survey panel design, composed of 5 interview rounds over 2 calendar years, allows researchers to determine how the status of participants' health status, income, employment, insurance coverage, health care resource use, and care payment are related. More specifically, the 2018 MEPS Household Component full year consolidated (FYC) and prescribed medicines event data files were used. FYC data used for this study included cohorts that were observed in the last 3 rounds of the 2017-2018 MEPS panel and the first 3 rounds of the 2018-2019 panel (in total 2017-2019). 29, 30 The FYC data file contains survey data from a sample of both families and individuals in selected communities across the country, chosen from a nationally representative subsample of households that participated in the previous year's National Health Interview Survey. During participant interviews, MEPS collects detailed information for each person in the household on several topic areas including demographic/characteristics, health conditions, health status, use of medical services, medical charges and source of payments, access to care, satisfaction with care, health insurance coverage, income, and employment. The prescribed medicines event file contains event-level data on prescribed medications including medication name, type, dosage, insurance type, drug expenditures, and other methods of payment. These data are collected first from survey respondents, and, after receiving consent from the respondent, more detailed information is collected from their pharmacies. 29, 30 This study was exempt from review by the institutional review board as MEPS is publicly available and deidentified data.

ELIGIBLE SAMPLE AND INCLUSION AND EXCLUSION CRITERIA
Noninstitutionalized US adults (aged 18 years and older) who responded to the question pertaining to vaccination status and filled a prescription at a community and/or mail order pharmacy were included in the sample. Respondents were excluded if they did not respond to questions concerning any of the additional variables observed.

MEASURES
The outcome variable was self-reported receipt of the influenza vaccine within the past year (variable name: ADFLST42). To collect these self-reported data, participants were asked to indicate whether (yes/no) they "had a flu vaccine in both age strata (< 65: 40.9% vs 55.8%; ≥ 65: 68.7% vs 74.3%; P < 0.001). Respondents aged 65 years and older also had greater proportions of vaccine receipt than those aged younger than 65 years (Table 1). Additionally, compared with community pharmacy users, mail order pharmacy users were more likely to be aged 65 years and older (P < 0.0001), be White (P < 0.0001), have a high income (P < 0.0001), have a chronic condition diagnosis (diabetes, cancer, or heart disease; P < 0.001), and have a usual source of care (P < 0.003).

INFLUENZA VACCINATION LIKELIHOOD
In the unadjusted model, community pharmacy users in both age strata were less likely to receive the influenza vaccine than their mail order pharmacy user counterparts (< 65 odds ratio [OR] = 0.55; 95% CI = 0.47-0.64; ≥ 65 OR = 0.76; 95% CI = 0.64-0.90). The adjusted odds ( Figure 2) for influenza vaccination were significantly lower among community pharmacy users than mail order pharmacy users among individuals aged younger than 65 years (OR = 0.71; 95% CI = 0.58-0.87) but not among those aged 65 years and older (OR = 0.87; 95% CI = 0.69-1.09). The results from the propensity score match analysis are consistent with the multivariable-adjusted weighted logistic regression model results (Supplementary Materials).
included in the study sample. A sensitivity analysis was conducted using propensity score matching (PSM). Additional details on this analysis can be found in the Supplementary Materials, available in online article. The family of procedures meant to handle complex survey data in SAS version 9.4 were used to conduct all analyses (SAS Institute).

COHORT DESCRIPTION
Of the 30,461 respondents assessed for eligibility, 18,350 were excluded, leaving 12,111 eligible respondents ( Figure 1). The study population included 8,074 respondents aged younger than 65 years and 4,037 respondents aged 65 years and older, who represented 95,930,349 and 40,163,276 weighted observations, respectively. Pharmacy users across both strata were majority White, had a high income (≥ 400% federal poverty level), lived in the South, and had a high school diploma/GED, with users aged younger than 65 years having a greater proportion of males and a lower prevalence of chronic conditions. Contrastingly, pharmacy users aged 65 years and older had a greater proportion of females and a greater prevalence of chronic conditions. Mail order users had a greater proportion of respondents who received the < 65 years (n = 7,304) ≥ 65 years (n = 3,091)  community pharmacy users aged younger than 65 years. 35 Even with suboptimal vaccination rates, our results supported previous findings that observed "vaccine-seeking behavior" among older adults, as adults aged 65 years and older had substantially higher vaccination rates than those aged 18-64 years. [31][32][33][34] Our results found pharmacy use type may influence vaccination likelihood differently than previously hypothesized. In the unadjusted model, community pharmacy users were less likely to receive the influenza vaccination than mail order pharmacy users in both age strata. Factors 95% CI = 1.06-1.59) and having a bachelor's degree and above (OR = 1.41; 95% CI = 1.14-1.74) significantly increased the likelihood of vaccination ( Figure 3).

KEY POINTS
Despite the general recommendation for influenza vaccinations to be received annually, we found influenza vaccination rates were less than 75% for all pharmacy user cohorts and age strata, with the lowest rate (40.9%) among

Liklihood of influenza vaccination
Aged 65 years and older

FIGURE 2 Odds of Influenza Vaccination Across All Variables by Age Strata (continued)
pharmacies may serve as a prime location for interventions to improve vaccination receipt. Although influenza vaccinations administered in the pharmacy setting have increased significantly over the years, overall vaccination rates are beginning to stagnate-suggesting that those already receiving their vaccination in the community pharmacy setting without prompting may have other enabling characteristics that increase their vaccination likelihood. This group, which often chooses the community pharmacy setting to receive their vaccine because of its convenience, ease, accessibility, and lower cost, is in the minority. 36 In fact, most people receiving their vaccine within a community pharmacy arrive with the intentions of doing exactly that, supporting that these sites may mostly be providing a more convenient vaccination location for those already intending to receive the vaccine. 36,37 Of those who already use pharmacist-administered vaccine services, community pharmacy users still have a decreased likelihood of receiving a pharmacist-administered vaccine in comparison with mail order pharmacy users. 38 Consequently, individuals specifically using the community pharmacy to receive prescription medications only are an optimal group for maximum impact of community pharmacist vaccination interventions, as they are less likely to have already been vaccinated.
In practice, many of the people who need influenza vaccines are regularly visiting a place that can meet their need-the community pharmacy. Through successful identification, recommendation, and offering of vaccinations by health care providers to individuals that receive their prescription medications in community pharmacies, pharmacists have the potential to increase vaccine rates. 39 Targeted community pharmacy interventions can increase opportunities to administer additional life-and cost saving vaccines for those who would not usually have access to or consider receiving them. In community pharmacies alone, pharmacists have administered almost 200 million COVID-19 vaccinations, demonstrating their appropriate training and ability to take advantage of opportunities to execute vaccine reminders and recommendations and to dispel misconceptions concerning vaccinations. 16, 40 As the United States continues to navigate COVID-19 vaccination schedules and immunizations for influenza and other vaccine-preventable illnesses, these efforts and potential for positive population health impact is monumental.
Mail order pharmacies have the potential to reduce barriers in cost and pharmacy access and many other challenges to medicine receipt for individuals that face disparities in health care access. 25 Our results indicate that health plans should feel confident that incentivizing mail order pharmacy use should not reduce the likelihood of influenza vaccination, particularly for those aged 65 years and older; that increased likelihood of vaccination included higher education, female sex, higher income, and having a diagnosis of asthma, heart disease, and/or diabetes. Alternatively, factors that decreased likelihood of vaccination included identifying as Black, younger age, and having no usual care provider. Mail order pharmacy users were more likely to be White, older, and more educated and to have a usual care provider and higher income, all characteristics that have been associated with this group in previous literature among other characteristics not observed in this study. 17,24,25 Controlling for the potential confounders in the multivariable-adjusted weighted logistic regression model (and PSM) made OR results more similar between mail order and community pharmacy users compared with the unadjusted analysis. However, when adjusting for sociodemographic, health status, and health access and utilization factors, differences between pharmacy type were reduced but not eliminated. Ultimately, community pharmacy users aged younger than 65 years were still significantly less likely to receive an influenza vaccine than mail order pharmacy users. These results are counterintuitive in that despite patients that use community pharmacies having greater access to pharmacist-administered vaccination services, they were still less likely to receive an annual influenza vaccine. 12,13

IMPLICATIONS
The persistently lower rate of influenza vaccination among community pharmacy users, particularly among those aged younger than 65 years, suggests that community This graphic shows the odds of influenza vaccination by analysis type and age strata for community pharmacy users in comparison with mail order pharmacy users. MWLR = multivariable-adjusted weighted logistic regression model.

FIGURE 3 Odds Ratio Comparison
Odds ratio (CI) Liklihood of influenza vaccination by analysis type compared with mail order pharmacy users influenza vaccination and identifies a prime health care setting for impactful intervention. It has additional strength in that it accounts for real-world factors that impact vaccination likelihood in a nationally representative population.

LIMITATIONS
Despite promising results, this study had notable limitations. First, MEPS provides users' pharmacy type and vaccination status but does not indicate the location of vaccine receipt. Because of this, we are unable to confirm whether the respondent had their vaccine administered by a pharmacist or in a pharmacy setting. The flu vaccination variable, along with several other variables, was also susceptible to recall bias from the respondent and does not specify the season of receipt (ie, 2017-2018, 2018-2019), only whether it was received in the past year. This does not allow us to report our results in the seasonal manner in which vaccination-related statistics are traditionally communicated. Nevertheless, the variable variety and panel design of MEPS survey data, featuring 5 rounds of interviews over 2 full calendar years, makes it possible to observe how the status of participants' health status, income, employment, eligibility for public and private insurance coverage, use of services, and payment for care are associated-something not comprehensively observable in most individual sets of data.
Second, the dichotomization of patients into community pharmacy and mail order user groups, although aligned with previous literature using MEPS, does not reflect the degree to which a patient uses mail order pharmacies. Indeed, a patient who uses mail order for one prescription and a community pharmacy for all others may be more similar to a patient who uses community pharmacy alone than a patient who uses mail order for all prescriptions. However, the structure of the MEPS pharmacy file does not allow for the calculation of the proportion of fills that derive from each pharmacy choice.
The final limitation is the inability to account for all potential confounding variables that influence both pharmacy type and vaccine receipt. For instance, this study was not able to address vaccine hesitancy, a hot-button issue right now, particularly with newer vaccines for COVID-19. Notably, this limitation was partly addressed by the PSM analysis, which supported the results found in the primary analytical approach.

Conclusions
Greater uptake of vaccinations could improve population health and health-related cost burden in the United States. Yet, despite the wide availability of influenza vaccines at those who choose mail order pharmacy are also those who are most likely to receive vaccinations, despite pharmacy choice. However, the potential for mail order pharmacies to serve as substitutes for community pharmacies, and therefore reduce opportunities for influenza vaccinations, is not supported by these results. We find that sociodemographic differences between patients who choose mail order over community pharmacies likely drive a person to also get vaccinated, in turn counterbalancing any reduced access facilitated by pharmacy choice. Although this study did not estimate the causal impact of using mail order pharmacy on influenza vaccination status, it does not appear that a shift in patients choosing to use mail order pharmacies should create concern from a public health perspective.
Notably, the impact that a shift to mail order pharmacy may have on the use of other health care services and interventions, or factors such as health literacy, personal health agency, propensity for follow-up with health care providers, and other aspects of health behavior, was not observed in this study. Furthermore, currently proposed policy changes that direct operation of the US Postal Service, a major servicer for prescription delivery, could decrease the reliability and efficiency of the US Postal Service in the future for those who rely on mail order pharmacy most heavily and consequently impact the associations observed in this study. 17 Additionally, in light of the COVID-19 pandemicrelated strain and unpredictability in online ordering and other mail delivery services, implications in mail order pharmacy could continue to fare a detrimental impact. 41 It should not be overlooked that additional independent factors can also influence an individual's choice in whether they decide to receive an influenza vaccine. In this study, people who chose to use mail order pharmacies to receive prescriptions were more likely to receive their annual influenza vaccine. However, personal characteristics attributed to mail order pharmacy users were generally associated with an increased likelihood of vaccination. Several results on the influence of sociodemographic, health status, and health access and utilization factors reflect what has been evidenced in previous literature that characterize vaccine immunization recipients and disparities in vaccine receipt. [26][27][28][42][43][44][45][46] Our results reinforce that targeted interventions for certain chronic conditions and sociodemographic groups would help to foster health equity and increase the likelihood of influenza vaccination for these populations. [43][44][45] To our knowledge, this study is the first of its kind to examine the relationship between pharmacy use type and influenza vaccination in the general population while also accounting for additional patient-level factors. Furthermore, it is one of few studies that both highlights disparities in This project did not receive funding from any agency in the public, commercial, or not-for-profit sectors. community pharmacies, those aged younger than 65 years were less likely than their mail order counterparts to receive the vaccination. Community pharmacies may serve as optimal sites for interventions to improve vaccination rates, as vaccinations are readily available at these sites and the patients frequenting them are most in need of vaccination. Additionally, specific groups based on sociodemographic, health, and health care access and utilization factors can also be targeted to improve influenza vaccination. Further research conducted on factors that influence pharmacy choice, vaccination likelihood, and the successful implementation of community pharmacy interventions could support these efforts.

DISCLOSURES
Dr Burbage was a fellow in the Real World Evidence, Population Health and Quality Research Postdoctoral Fellowship Program in collaboration with University of North Carolina Eshelman School of Pharmacy and Pharmacy Quality Alliance, and supported by Janssen Scientific Affairs at the time of this study. She is now employed by Janssen Scientific Affairs. Dr Parikh is an employee of Pharmacy Quality Alliance. Dr Campbell was employed by Pharmacy Quality Alliance at the time of the study. He is now employed by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Dr Ramachandran has received an unrelated research contract with Pharmacy Quality Alliance. Dr Gatwood has received vaccine-related research grants from Merck & Co. and GlaxoSmithKline unrelated to this project and consulting fees for a vaccine-related expert panel with Merck & Co. unrelated to this manuscript and is an advisory board member with Janssen Scientific Affairs. Dr. Urick was employed by the UNC Eshelman School of Pharmacy at the time of this writing and is currently employed by Prime Therapeutics. He has received community pharmacy-related consulting fees from Cardinal Health and Pharmacy Quality Solutions unrelated to